The current proposal requests continuing support for a multidisciplinary General Clinical Research Center involving research on both adults and children. The objective of the Clinical Research Center at the University of Michigan is to perform meritorious research in humans, which leads to an improved understanding of human biology, the prevention of disease, the elucidation of disease processes, or novel approaches to the diagnosis and management of diseases in humans. In addition, the Clinical Research Center aims to function as: (a) an institutional resource as a focal point for training in clinical research and (b) as a national and state resource to complement patient care by the discovery of new knowledge to assist and improve the diagnosis and management of patients. Our work to achieve these goals during the past six years includes a series of important advances and achievements which are already contributing to the improvement of health care. In addition, many trainees have been exposed to the Clinical Research Center environment. During the next five years we propose to continue to work towards our goal with over 160 separate clinical research protocols which involve studies ranging from physiological and biochemical studies of normal human function, studies of the molecular pathology and pathophysiology of human disease states, clinical trials to modify human disease states with both established and experimental forms of therapy, and pharmacokinetic studies to understand the metabolism and distribution of specific drugs. To support this activity requires an inpatient service, outpatient service, computing facility, Biostatistical Consulting Service, Core Laboratory with a new Human Cell Genetics Facility, Administrative Service, and a complex series of physical facilities and equipment. The investigators involved in the research include individuals from the Departments of Internal Medicine, Surgery, Pediatrics, Human Genetics, Pharmacology, Psychiatry, Physiology, Biological Chemistry, Neurology, Dermatology, Radiology, Physical Medicine and Rehabilitation, Radiation Therapy, Otorhinolaryngology, School of Public Health, School of Nursing, and College of Pharmacy. A substantial training program is proposed involving Clinical Associate Physicians, fellows, Internal Medicine residents, medical students, nursing students, dietetic students and dietitians. It is anticipated that the research proposed will bring advances in the understanding of normal human function and disease states in many fields. Continuing support of the Clinical Research Center will provide a stable focus for clinical research at the University of Michigan.